title: Phosphodiesterase-5 inhibitors.
abstract: Nitric oxide (NO) signaling plays a key role in modulating vascular tone and remodeling in the pulmonary circulation. The guanylate cyclase/cyclic guanylate monophosphate-signaling pathway primarily mediates nitric oxide signaling. This pathway is critical in normal regulation of the pulmonary vasculature, and is an important target for therapy in patients with pulmonary hypertension. In the pulmonary vasculature, degradation of cGMP is primarily regulated by PDE-5, and inhibition of this enzyme has important effects on pulmonary vasculature smooth muscle tone. Large randomized placebo-controlled trials of PDE-5 inhibitors demonstrated improved exercise capacity, hemodynamics and quality of life in adult patients with PAH. This chapter will discuss the mechanisms of NO signaling in the vasculature, characteristics of the PDE5-inhibitors approved for treatment of PH, and review available data on the use of phosphodiesterase inhibitors in PH.
authors.affiliation: Pulmonary Vascular Disease Program, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA, bcockrill@partners.org.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Cockrill
authors.forename: Aaron B
authors.initials: AB
authors.lastname: Waxman
mesh_terms: D000818:Animals; D017869:Cyclic GMP-Dependent Protein Kinases / Q000502:physiology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D009569:Nitric Oxide / Q000502:physiology; D058986:Phosphodiesterase 5 Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction; D013318:Stroke Volume / Q000187:drug effects
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D009569:Nitric Oxide; D017869:Cyclic GMP-Dependent Protein Kinases